Since World War II, there have been dramatic increases in metabolic, immune, and cognitive diseases, including obesity, diabetes, asthma, allergies, inflammatory bowel disease, and autism. Their incidence has risen, first in the industrialized world and more recently in developing countries (1). In addition to the health effects, there are enormous costs of these diseases: Obesity costs $2.0 trillion and diabetes costs $1.3 trillion per year globally (1–3). As these diseases advance in developing countries, the problem is worsening rapidly. The cost, to health and economies, is becoming unsustainable, with care of chronically ill adults competing with the proper care for the next generation. Are all these distinct diseases independent, or is there a common underlying factor? We believe that changes in the human microbiota occurring concomitantly with industrialization may be the underlying factor. The changes involve the loss of our ancestral microbial heritage to which we were exposed through millions of years of evolution.